Stories about the people, science and research of the Medical Research Council.

Working at the edge: a Q&A with Doug Turnbull

by Guest Author on 3 December 2012

Doug Turnbull

The University of Newcastle’s Doug Turnbull is part of a team (with Professors Mary Herbert and Alison Murdoch) that is developing a technique to prevent inherited genetic conditions called mitochondrial diseases. ‘Mitochondrial transfer’ replaces a woman’s faulty mitochondria with those of a healthy donor, and combining the technique with IVF could mean affected women no longer pass on these diseases.

As the public consultation on whether to change the law to allow mitochondrial transfer draws to a close, Katherine Nightingale talks to Doug about the technique, why it’s needed and what it’s like to be working in a potentially legislation-changing field.

Will we have heard of any of these mitochondrial diseases?

The diseases affect the mitochondria — the ‘batteries’ of the cell that produce the energy cells need to function properly. You might not have heard of them; some, such as Leigh’s syndrome, have been known for many years among doctors and researchers but the collective term of mitochondrial diseases isn’t well known among the public, even though around 1 in 6,000 children is born with some kind of mitochondrial disease. The diseases most affect the parts of the body that use the most energy: the brain and nervous system, muscles and other major organs such as the heart and liver.

The intriguing thing about mitochondria is that they have their own DNA, separate to the DNA in a cell’s nucleus. The affected genes in mitochondrial diseases are in this mitochondrial DNA, meaning they are inherited differently to other genetic diseases — only mothers pass them on to their children through their eggs.

Why can’t you just treat mitochondrial diseases?

Treating a mitochondrial disease is difficult — we can really only treat its symptoms, which means vitamin therapy and techniques to conserve energy. That’s why we want to prevent them in the first place.

We are trying though; we’re collaborating with drug companies to look at agents that could improve the function of abnormal mitochondria. We’re very aware that we mustn’t forget about the people who already have the disease.

Can you explain the transfer technique?

We’re focusing on a technique called pronuclear transfer. This means that the woman’s egg is fertilised in the normal way via IVF and then its nuclear DNA is removed and put into a donor embryo that has had its own nuclear DNA removed. So you end up with an embryo that has nuclear DNA from the parents (around 23,000 protein-making genes) and mitochondrial DNA from the donor (11 protein-making genes). This donor mitochondrial DNA is now in the ‘germline’ — it will be passed on to future generations.

Other research groups are trying another technique called spindle transfer that uses eggs rather than embryos — part of our research is to compare the safety and effectiveness of these techniques.

In our technique embryos come either from egg sharers or altruistic donations. If we start treating patients, I don’t imagine that there will be a problem finding donors of mitochondria — even a woman’s friends might donate eggs.

Why is it needed?

For me it’s all about offering women who carry mitochondrial mutations reproductive choice, in the same way that everyone else makes reproductive choices. At the moment there are some choices that women with mitochondrial disease can make, such as a biopsy at 11 weeks of pregnancy to determine whether the foetus has mitochondrial disease. There’s also a technique called preimplantation genetic diagnosis, which is used in conjunction with IVF to test embryos in their first few days so that the woman and her partner can decide which embryos to transfer into her womb.

I really believe in offering these choices. But we see some women, maybe 10–20 a year, who have such a high level of mutations that these options won’t work. For these women replacing the mitochondrial DNA is the only option for having a healthy child.

An illustration of a mitochondrion (Credit: Flickr/hasserin)

How far have you got with the research, and what’s the legal situation at the moment?

We’re assessing the safety and effectiveness of the procedure in human embryos. Under current law, we can do this research but we can’t implant the embryos into women. The idea is that we research the technique in parallel with the consultation process, so the research can be ready if and when the law is.

The public consultation about the technique is just about to end and the report will be going to Government in March next year. I’m not exactly sure how long the process in Parliament could take, but if the law is changed it won’t be for some time — it’s a complex matter.

What would you say to people who think the law shouldn’t be changed?

My view is that to prevent one child with mitochondrial disease would be worth it. I find it very emotional thinking about what my patients go through, particularly the younger ones. If there is something we can do to help, why wouldn’t we?

Did you ever think you’d be involved in research that could result in the law being changed?

No, never. It’s changed my perspective and shown me how important it is to engage the public — and politicians. These are complex issues that need more than a knee-jerk response. This has really opened my eyes and we’ve taken an active role in explaining things to the public and particularly to our patients. We run a national clinic for people with mitochondrial disease here, and patients respond well to the idea.

Obviously I’m biased but I’ve been to a few public meetings about this and there’s always been a more positive than negative response. I’ve never done anything like this before and I do find it challenging. But I remain hopeful. I hope we’ll be able to do this, but I’ve got no idea whether it will happen.

Media reports have referred to children resulting from the technique as ‘three-parent babies’. What do you think of the phrase?

It’s a double-edged sword really. If newspaper headline writers hadn’t used it, we wouldn’t have had as much publicity, but having said that, it’s clearly inaccurate.

We’re talking about 11 genes in the mitochondria that make proteins, versus around 23,000 in the nucleus. And the mitochondrial genes are nothing to do with characteristics. I think people are seeing through this, and recognising that we’re talking about a small amount of DNA. Also, I think the parents are those that bring up the child.